The aims of this project are based on the following findings: (1) We showed that bladder transitional cell carcinoma (in rats and in man) has greatly elevated (10-fold) galactosyl transferase enzyme activity in the cell surface membrane. (2) In cell culture of bladder carcinoma, we showed this enzyme to consist of 2 isozymes of about equal activity. (3) Vitamin A (retinoids) inhibit bladder carcinogens in rats. (4) We have results indicating that retinoids caused lowered gal transferase activity in our bladder carcinoma cell culture system. Our specific aims, then, are: (1) To determine whether normal bladder epithelium lacks one of the gal transferase isozymes and, if so, which one. (2) To determine whether the increase in gal transferase in bladder carcinoma cells is caused by elevation of the (hypothetical) cancer-associated isozyme, or the normal isozyme or both. (3) To attempt a purification to a high degree of purity of the isozymes and to characterize their properties especially with a view to determining whether they are glycoproteins, similar to serum gal transferase. (4) To confirm that vitamin A lowers gal transferase in bladder cancer cells in culture, to determine whether this lowering is in the (hypothetical) isozyme which may be associated specifically with the cancer cells. (5) To study the properties of this inhibition: time and concentration dependence, types of retinoids, as well as kinetics of decrease and possible reappearance after removal of retinoid. The uptake of labeled retinol into cells and subcellular location. (6) To study a possible mechanism whereby vitamin A may lower gal transferase activity in the following way: the gal transferase is probably a glycoprotein. It is known that retinol affects glycoprotein synthesis and could, therefore, shift the synthesis of the isozymes from the cancer-related to the normal isozyme. The relationship between the effect of retinoids on inhibition of bladder carcinogens, on gal transferase activity and on glycoprotein synthesis would thus become amenable to investigation.